The goal of this project is to develop improved methods for diagnosing and treating the ocular complications of the acquired immunodeficiency syndrome (AIDS). This project encompasses clinical trials evaluating new diagnostic and therapeutic approaches for patients with AIDS-related eye disorders, as well as natural history studies of patients with Cytomegalovirus (CMV)retinitis. Cytomegalovirus (CMV) retinitis is the most common intraocular infection in patients with AIDS and tends to occur after CD4+ cell counts decrease to less than 50 cells per microliter. Although anti-CMV therapy with ganciclovir, foscarnet sodium, or cidofovir initially leads to inactivation of the retinitis, the disease progresses in almost all patients despite continued therapy because of inadequate control of the replicating virus. Recent case reports have shown that treatment with highly active antiretroviral therapy, commonly consisting of protease inhibitors and nucleoside analogs, has led to decreased human immunodeficiency virus (HIV) loads and increased CD4+ counts. The NEI has been conducting a prospective clinical trial to determine whether maintenance anti-CMV medications can be safely discontinued in patients with stable CMV retinitis. The study was also designed to determine whether discontinuing anti-CMV therapy will increase HIV load or cause intraocular inflammation. Recruitment of the initial phase of the trial has been completed. To date, no patient has experienced CMV progression or any other study endpoint and these results were published. Unexpectedly, the majority of the patients in this trial were observed to have ocular inflammation related to their immune recovery, a phenomenon termed immune recovery uveitis. The details of this syndrome observed in patients participating in this trial were recently published. The protocol will continue to examine the durability of highly active antiretroviral therapy in maintaining increased CD4+ counts and inactive CMV retinitis.